Human pituitary somatotropes express transforming growth factor-α and its receptor

Transforming growth factor-α (TGF-α) is a growth-regulatory peptide produced by a variety of transformed and non-transformed cells. Among non-transformed cells, TGF-α has been identified in the prolactin (PRL)- and GH-secreting cells of the bovine anterior pituitary gland. In this report, we have examined the expression of TGF-α in human anterior pituitary glands by Western analysis and immunohistochemistry. For the Western analysis, human pituitary glands were extracted in acid/ethanol, an acetic acid-soluble fraction was ether-precipitated and dialysed, and TGF-α was partially purified by C18 chromatography. TGF-α was then identified by immunostaining of Western transfers. Anterior pituitary extracts exhibited a major band(s) migrating at 19 kDa that was immunoreactive with a monoclonal antibody directed against the mature TGF-α. However, no evidence of the fully processed 6 kDa TGF-α was observed. We next identified TGF-α by immunohistochemistry. Using both monoclonal and polyclonal antibodies, specific immunoreactivity was identified in a population of secretory cells in the anterior pituitary gland. Using antibodies specific for the COOH and NH3 terminals of the TGF-α precursor, a comparable number of TGF-α-positive cells were found to contain TGF-α precursor sequences. These results indicate that the 19 kDa form of TGF-α expressed in the human pituitary gland may exist as the transmembrane form. We next sought to determine which cells express TGF-α in a human male pituitary gland. On frontal sections, TGF-α-immunopositive cells were evenly distributed in a manner and number indistinguishable from GH-immunopositive cells. By contrast, PRL-immunopositive cells in midfrontal sections were largely restricted to the lateral wings and extended dorsally to the neural lobe. TGF-α was positively co-localized to GH-immunopositive cells but not in PRL-immunopositive cells by immunostaining of consecutive sections. TGF-α-immunopositive cells were also immunopositive for the epidermal growth factor receptor, indicating that TGF-α has the capacity for autocrine action in the human pituitary gland. These results indicate that TGF-α is expressed in the human anterior pituitary gland and it is not proteolytically processed into the mature 6 kDa form. In addition, immunohistochemistry of an adult male human pituitary gland indicates that TGF-α is expressed in somatotropes and has the capacity for autocrine action. Journal of Endocrinology (1994) 141, 547–554